Method Verification. The How M.L. Jane Weitzel ALACC Chair

Transcription

1 Method Verification The How M.L. Jane Weitzel ALACC Chair

2 The What Released early lacc_guide_2008.pdf

3 Meet ISO Requirement

4 Categories of Methods The six categories of chemical analytical methods are: 1. Confirmation of Identity, a method that ensures a material is what it purports to be or confirms the detection of the target analyte. 2. Quantifying an analyte at a low concentration. 3. Determining if an analyte is present above or below a specified, low concentration (often called a Limit Test). The specified concentration is close to the LOQ.

5 Categories of Methods 4. Quantifying an analyte at a high concentration. 5. Determining if an analyte is present above or below a specified, high concentration (often called a Limit Test). The specified concentration is substantially above the LOQ. 6. Qualitative test.

6 Tables 2-6 Requirements of Method Verification for the Six Categories of Chemical Test Methods (Tables 2 6)

7 Category 1: Confirmation of Identity

8

9 ISO Technical Specification ISO/TS 21748, Guidance for the use of repeatability, reproducibility and trueness estimates in measurement uncertainty estimation

10 ISO/TS Template for Verification ISO is a thorough guide to verifying a method. The examples will be based on ISO 21748

11 Specification for the Method The results of collaborative study yield performance indicators (sr, sr) and, in some circumstances, a method bias estimate, which form a specification for the method performance. In adopting the method for its specified purpose, a laboratory is normally expected to demonstrate that it is meeting this specification.

12 Repeatability In most cases, this is achieved by studies intended to verify control of repeatability and of the laboratory component of bias, and by continued performance checks (quality control and assurance)

13 Many added benefits Method verification Estimate of Uncertainty Better understanding of the method

14 Equation y= μ +δ +B+ Σcix i +e

15 Equation Components y = µ + δ + Β + e + Σ c i x i Result = ideal result + method bias + lab bias + repeata bility + sum of effects NOT included in collaborative study

16 What if your method was not collaboratively studied? The approach described by ISO is still relevant. Intermediate precision could be substituted for reproducibility Fewer variables would be included in intermediate precision study than during a reproducibility study There would be more effects included in Σ c i x i The approach provides a detailed, organized procedure for identifying and evaluating these effects

17 Method Bias δ method bias Collaborative Study Note: the study may not include this component

18 Lab Bias Β lab bias Collaborative Study s L 2 s R2 = s L2 +s r 2 Thus s L 2 = s R 2 - s r 2

19 Repeatability e repeatability Collaborative Study s r 2

20 Effects NOT included Σ c i x i sum of effects NOT included in collaborative study Examine the equation and procedure.

21 Table Summary y µ δ Β e Σ cix i Result Ideal result Method bias Lab bias Repeatability Sum of effects not included in collaborative study Source of Specification for the method Collaborative Study. Note: the study may not include this component Collaborative Study sl2 s R2 = s L2 +s 2 r Thus s L2 = s R2 - s 2 r Collaborative Study s r 2 Examine the equation and procedure

22 Method Bias δ method bias Collaborative Study Note: the study may not include this component. The study may include method bias, if for example the results are corrected for a known method bias. The procedure for assessing method bias is included in the ISO standard in detail in Incorporating Trueness Data. (Uncertainty associated with CRV becomes important)

23 Repeatability - Equation e repeatability Collaborative Study s r 2 Do repeatability study in lab. Calculate s w. Compare to s r2 using the F test.

24 Bias Often accuracy must be verified Terminology bias Can use same data from repeatability If Certified Reference Material is available

25 Lab Bias Β lab bias Collaborative Study s L 2 s R2 = s L2 +s r 2 Thus s L 2 = s R 2 - s r 2

26 Bias Specification Follows ISO Guide 33 Δ = m - µ = mean - CRV Δ < 2σ D Δ < 2 (s R2 s L2 = s R2 - s r 2 - s r2 + s w2 /n)

27 n Choose n so that the uncertainty of the bias is not significant choose n such that the uncertainty s w2 /n < 0.2s R Good rule of thumb uncertainties less than 0,2 s R lead to changes of under 0,02 s R in the overall uncertainty estimate.

28 Σ c i x i Look at equation to identify any source of uncertainty that was not included in the collaborative study. It is often convenient to consider each of the three factors the sample, the laboratory and the method when identifying gross uncertainties

29 Specificity If your sample is not identical to those included in the collaborative study or method validation, you must assess the impact of the differences. AOAC Food triangle can be useful

30 Useful Table 8 in ALACC Method Verification Guide Lists Parameter The difference from the validated method Required Equivalence Study

31 Useful Table 8

32 Table 8 Example

33 Uncertainty For a collaboratively studied method and if you follow the process from ISO 21748, you will also end up with an estimate of the uncertainty for the method.

34 Table Summary y µ δ Β e Σ cix i Result Ideal result Method bias Lab bias Repeatability Sum of effects not included in collaborative study Source of Specification for the method Collaborative Study. Note: the study may not include this component Collaborative Study sl2 s R2 = s L2 +s 2 r Thus s L2 = s R2 - s 2 r Collaborative Study s r 2 Examine the equation and procedure

35 Examples